JP7240336B2 - Containers for cell medicine formulations - Google Patents

Description

TECHNICAL FIELD The present invention relates to a cell pharmaceutical preparation container used for storing a cell pharmaceutical preparation and administering it to a patient, and a method for preparing the cell pharmaceutical preparation.

In the medical field, when administering drugs containing pharmaceutical compounds or vitamins to patients, the drug bag containing the drug solution is suspended from the hook of the drip stand, and the drug solution drips from the drug bag by gravity. , the drug solution is directly introduced into the patient's body through an injection needle placed in the patient's venous artery. In recent years, various administration forms have been reported in addition to the conventional administration methods described above.

For example, in US Pat. No. 5,200,000, a portion of a first syringe having inscriptions relating to dosage relative to patient weight is fed into a medicament container, the first syringe is filled to the dosage, and the medicament is dispensed. A method of administration to a patient is described. According to US Pat. No. 5,400,000, this method does not require the calculation or correlation of drug dose to patient weight.

Further, Patent Document 2 discloses a drug solution bag having a bag body having a chamber capable of enclosing a drug solution, in which a marker indicating the patient's weight corresponding to the dose of the drug solution to be administered is attached to the outer surface of the bag body. It is stated that it may be In Patent Document 2, after confirming the patient's weight, the medical staff clamped the bag body with a clip according to the markers of the drug solution bag of this embodiment, and prepared the drug solution in a dose according to the patient's weight. Above, administering to a patient is described.

Furthermore, Patent Document 3 describes a medical container provided with a first scale display portion that displays the amount of liquid in the soft bag and a second scale display portion that displays the amount of liquid in the bag above the liquid level. It is described that the medical staff can administer the drug to the patient after confirming the presence or absence of co-injection with other drugs using the second scale display part of the medical container as an index.

Japanese Patent Publication No. 2015-508321 JP 2017-164421 A JP 2007-260252 A

When administering a cell pharmaceutical formulation containing cells used in cell therapy to a patient, the cell pharmaceutical formulation is a cell suspension. In consideration of aggregation, an appropriate dose of cells (cell number and cell density) according to the patient's body weight must be accurately administered to the patient.

Therefore, the present inventors have found that as a method of administering to a patient an appropriate dose of cells according to the weight of the patient, the number of cells according to the weight of the patient is obtained from the first container containing the cell pharmaceutical preparation. A method of removing the cells from the formulation with a syringe, transferring to another second container, diluting to an appropriate cell density with physiological saline, and administering the entire amount in the second container to the patient was examined. However, in this method, when the cell pharmaceutical preparation is transferred from the first container to the second container via the syringe, the cells remain in the vicinity of the lead-out portion in the syringe, causing the cells in the second container to A problem was found that the cells may die due to the decrease in the number and the pressure when the cell suspension is drawn out from the syringe. In addition, the inventors have also found a problem that the cell density in the second container cannot be properly adjusted because the physiological saline remains in the syringe even when diluting with the physiological saline. Therefore, the administration methods described in Patent Documents 1 to 3 were further investigated in order to solve the above problems.

A first syringe having a labeling related to dosage relative to patient weight described in U.S. Pat. There is a problem that the cells are killed by the pressure when the liquid is introduced. Furthermore, in the case of cell pharmaceutical preparations, cells settle and aggregate over time, so it is necessary to allow the inside of the container to flow. space cannot be retained in the syringe, there is a problem that an appropriate cell density cannot be maintained during administration.

In the drug solution bag described in Patent Document 2, it is possible to divide the drug solution in the drug solution bag into doses according to the weight of the patient by clipping the drug solution bag. , the cells in the drug solution bag precipitate and aggregate over time. Therefore, even if an attempt is made to flow the entire cell pharmaceutical preparation by kneading the entire container, it is impossible to flow the entire cell pharmaceutical preparation because the drug solution bag is sandwiched between clips. There is a problem that the clip comes off from the drug solution bag when a sufficient pressure is applied.

In addition, the medical container described in Patent Document 3 has a first scale display portion that displays the amount of liquid in the soft bag and a second scale display portion that displays the amount of liquid in the bag above the liquid level, and the cell suspension is displayed. Although it is possible to confirm the presence or absence of co-injection with drugs other than turbid liquid, there is a problem that there is no means for confirming an appropriate dose of cells according to the patient's body weight.

In view of the above problems, the present invention provides a method for administering a cell pharmaceutical preparation to a patient by accurately grasping an appropriate dose of cells according to the patient's body weight and administering the preparation to the patient with a simple operation. The aim is to provide an enabling means.

Surprisingly, the present inventors found that a container for cell pharmaceutical preparations having the following features enables accurate determination of an appropriate dosage of cells according to the patient's body weight and administration to the patient through a simple operation. In addition, the present inventors have also found a method for preparing a cellular pharmaceutical preparation that can be administered to a patient with a simple operation by using the container for cellular pharmaceutical preparation, and completed the present invention.

(1) A cell pharmaceutical preparation container,
a container body having an internal space capable of holding a liquid;
a lead-out portion that communicates with the internal space of the container body;
The container body includes a first scale display portion for displaying the dose of the cell pharmaceutical preparation corresponding to the weight of the patient or subject to be administered,
The container, wherein the dose of the cell pharmaceutical preparation suitable for the patient's or subject's body weight can be visually recognized depending on whether or not the liquid surface position in the container body is positioned at the first scale display.
(2) The container according to (1), wherein the numerical value of the first scale display portion is displayed so as to increase toward the lead-out portion of the container body.
(3) Further, the container main body has a second scale display portion for displaying the amount of liquid for diluting the cell pharmaceutical preparation with a pharmaceutically acceptable drug, and the liquid surface position in the container main body is the above-mentioned The container according to (1) or (2), wherein the cell concentration of the cell pharmaceutical preparation to be administered to the patient or subject can be visually recognized depending on whether the container is positioned at the scale display part of 2.
(4) Further, the container body has a third scale display portion for displaying the amount of liquid to be filled with the cell pharmaceutical preparation, and the liquid surface position in the container body is positioned at the third scale display portion. The container according to any one of (1) to (3), wherein the number of cells of the cell pharmaceutical preparation to be introduced into the container body can be visually confirmed depending on whether the container is
(5) Further, the container body has a fourth scale display portion for displaying the amount of liquid in the container, and depending on whether or not the liquid surface position of the container body is positioned at the fourth scale display portion, The container according to any one of (1) to (4), wherein the amount of the cell pharmaceutical preparation remaining in the container body can be visually confirmed.
(6) The container according to (5), wherein the numerical value of the fourth scale display portion is displayed so as to decrease toward the lead-out portion of the container body.
(7) Further, the container main body has a fifth scale display portion for displaying the number of cells of the cell pharmaceutical preparation administered to the patient or subject, and the liquid surface position in the container main body is the fifth scale. The container according to any one of (1) to (6), wherein the number of cells of the cell pharmaceutical preparation administered to the patient or subject can be visually confirmed depending on whether or not the container is positioned on the display portion.
(8) The container according to (7), wherein the numerical value of the fifth scale display portion is displayed so as to increase toward the lead-out portion of the container body.
(9) The container main body has a second scale display portion for displaying the amount of liquid for diluting the cell pharmaceutical preparation with a pharmaceutically acceptable drug, and a third scale display portion for displaying the amount of liquid for filling the cell pharmaceutical preparation. and a scale display part of
The cell concentration of the cell pharmaceutical preparation to be administered to the patient or subject can be visually recognized depending on whether the liquid surface position in the container body is positioned at the second scale display portion,
The number of cells in the cell pharmaceutical preparation to be introduced into the container body can be visually recognized by checking whether the liquid surface position in the container body is positioned at the third scale display portion,
The container according to any one of (1) to (8), wherein the second scale display portion is provided on a line parallel to the third scale display portion.
(10) The container according to any one of (1) to (9), further comprising an introduction portion that communicates with the internal space of the container body.
(11) The container according to (10), wherein the lead-in portion is provided at the upper end portion of the container body facing the lead-out portion.
(12) The container according to any one of (1) to (11), wherein the container body is made of a flexible material.

(13) A method for preparing a cell pharmaceutical preparation,
A container body filled with a cell pharmaceutical formulation and having an internal space capable of holding a liquid, a lead-out portion communicating with the internal space of the container body, and a patient or subject body weight to be administered provided in the container body. and a second scale display provided on the container body for displaying the amount of liquid for diluting the cell medicinal preparation with a pharmaceutically acceptable drug. The above method, comprising the step of filling a cell pharmaceutical preparation container having a portion with a pharmaceutically acceptable drug until the liquid level reaches the second scale display portion of the container body.
(14) A method for preparing a cell pharmaceutical preparation,
A container body having an internal space capable of holding a liquid; a lead-out portion communicating with the internal space of the container body; a first scale display portion for displaying; a second scale display portion for displaying the amount of liquid for diluting the cell medicine preparation with a pharmaceutically acceptable drug provided on the container body; a container for cell medicinal preparation having a third scale display for indicating the amount of liquid to be filled with the cell medicinal preparation, and fill the cell medicinal preparation until the liquid level reaches the third scale display of the container body. filling;
filling the container filled with the cell pharmaceutical preparation with a pharmaceutically acceptable drug until the liquid level reaches the second scale display portion of the container body.

This specification includes the disclosure of Japanese Patent Application No. 2018-026959, which is the basis of priority of the present application.

According to the container for cell pharmaceutical preparation of the present invention, it is possible to accurately grasp the appropriate dose of cells according to the weight of the patient and to administer the cells to the patient with a simple operation. In addition, according to the method for preparing a cell pharmaceutical preparation of the present invention, a cell pharmaceutical preparation that can be administered to a patient can be prepared by a simple operation.

FIG. 1 is a diagram showing a cell pharmaceutical formulation container according to a first embodiment of the present invention. FIG. 2 is a diagram showing a state in which the cell pharmaceutical preparation container according to the first embodiment of the present invention is suspended and the cell pharmaceutical preparation is accommodated in the internal space. FIG. 3 shows that the cell pharmaceutical preparation container according to the first embodiment of the present invention is suspended, and the cell pharmaceutical preparation is stored in the internal space as shown in FIG. 2, and then the cell pharmaceutical preparation is administered to the patient through the outlet. It is a figure which shows the state when. FIG. 4 shows a state in which the cell pharmaceutical preparation container according to the first embodiment of the present invention is suspended, and the internal space is filled with a high-concentration cell pharmaceutical preparation until the liquid level reaches the third scale display. It is a figure which shows a state. FIG. 5 shows that the cell pharmaceutical preparation container according to the first embodiment of the present invention is suspended, and the internal space is filled with a high-concentration cell pharmaceutical preparation as shown in FIG. FIG. 10 is a diagram showing a state in which the cell pharmaceutical preparation is prepared by further filling and mixing until the liquid surface reaches the second scale display. FIG. 6 is a diagram showing a cell pharmaceutical formulation container according to a second embodiment of the present invention. FIG. 7 is a diagram showing a cell pharmaceutical formulation container according to a third embodiment of the present invention. FIG. 8 is a schematic diagram showing an example of a hollow fiber separation membrane module.

Embodiments of the present invention will be specifically described below, but the following description is for facilitating understanding of the present invention, and the scope of the present invention is not limited to the following embodiments. Other embodiments in which a person skilled in the art appropriately replaces the configurations of the following embodiments are also included in the scope of the present invention.

<Terms, materials>
A cell pharmaceutical preparation is a pharmaceutical preparation containing medically and/or pharmaceutically acceptable cells, specifically, medically and/or pharmaceutically acceptable cells and a pharmaceutically acceptable drug A pharmaceutical formulation comprising For the cell pharmaceutical preparation, it is preferable to use the cell pharmaceutical preparation container according to the present invention, which will be described later. In addition, in this specification, a "container" may be replaced with a "bag" and demonstrated.

In addition, cell pharmaceutical preparations may optionally contain salts, vitamins, amino acids, polysaccharides, dimethyl sulfoxide, buffers, albumin, medium, cell cryoprotectant CP-1 (manufactured by Kyokuto Pharmaceutical Co., Ltd.), and BAMBANKER. (manufactured by Lymphotech), STEM-CELLBANKER (manufactured by Nippon Zenyaku Kogyo Co., Ltd.), ReproCryo RM (manufactured by ReproCryo), CryoNovo (manufactured by Akron Biotechnology), MSC Freezing Solution (manufactured by Biological Industries), CryoStor (HemaCare) made), etc.

The medium in the present invention is not particularly limited as long as it is a medium composed of a component composition that allows cells to survive. 's Modified Dulbecco's Medium), Medium 199 medium, Eagle MEM medium, αMEM medium, DMEM medium (Dulbecco's Modified Eagle's Medium), Ham F10 medium, Ham F12 medium, RPMI 1640 medium, Fischer's medium, And these mixed media (e.g., DMEM / F12 medium (Dulbecco's Modified Eagle's Medium / Nutrient Mixture F-12 Ham)), CHO-S-SFM II (Life Technologies Japan Co., Ltd.), Hybridoma-SFM (Life Technologies Japan Co., Ltd.), eRDF Dry Powdered Media (Life Technologies Japan Co., Ltd.), UltraCULTURE ^™ (BioWhittaker), UltraDOMA ^™ (BioWhittaker), UltraCHO ^™ (BioWhittaker), UltraMDCK ^™ (BioWhittaker), etc.) can. Media such as STEMPRO (registered trademark) hESC SFM (Life Technologies Japan Co., Ltd.), mTeSR1 (Veritas), and TeSR2 (Veritas) can be used.

In addition to cells, cell pharmaceutical preparations contain various additives for increasing storage stability, isotonicity, absorption and/or viscosity, such as emulsifiers, dispersants, buffers, preservatives, and wetting agents. agents, antioxidants, chelating agents, thickeners, gelling agents, pH adjusters and the like. Examples of the thickening agent include, but are not limited to, HES, dextran, methylcellulose, xanthan gum, carboxymethylcellulose, hydroxypropylcellulose, and the like. The concentration of the thickening agent depends on the selected thickening agent, but can be arbitrarily set within a concentration range that achieves the desired viscosity while being safe when administered to a patient or subject.

Furthermore, the cell medicine formulation may contain immunosuppressants, antibiotics, albumin preparations, vitamin preparations, anti-inflammatory agents, etc., which are pharmaceutically active ingredients. Examples of the anti-inflammatory agent include, but are not limited to, 5-aminosalicylic acid preparations, steroid preparations, immunosuppressants, biological preparations, and the like. Examples of the above 5-aminosalicylic acid preparations include, but are not limited to, salazosulfapyridine and mesalazine. Examples of the above steroid preparations include, but are not limited to, cortisone, prednisolone, methylprednisolone, and the like. Examples of the immunosuppressive agents include tacrolimus, cyclosporine, methotrexate, azathiprine, 6-mercaptopurine, etc. Examples of the biological agents include infliximab, adalimumab, ustekinumab, secukinumab, and ixekizumab. , brodalumab, tocilizumab, vedolizumab, filgotinib, golimumab, certolizumab pegol, abatacept, etanercept, and the like.

The pH of the cell pharmaceutical preparation of the present invention can be around neutral pH, for example, pH 6.5 or higher or pH 7.0 or higher, or pH 8.5 or lower or pH 8.0 or lower, It is not limited to these.

The volume (mL) of the cell medicinal preparation should be the cell concentration (cells/mL) at which the safety of the patient or subject has been confirmed when the cell medicinal preparation is administered to the patient or subject. capacity, which is the capacity per bag. The volume of the cell pharmaceutical preparation is not particularly limited, but is, for example, 1 mL or more, 2 mL or more, 3 mL or more, 4 mL or more, 5 mL or more, 6 mL or more, 7 mL or more, 8 mL or more, 9 mL or more, 10 mL or more, 15 mL or more, 20 mL or more, 25 mL or more. 30 mL or more, 35 mL or more, 40 mL or more, 45 mL or more, 50 mL or more, 55 mL or more, 60 mL or more, 65 mL or more, 70 mL or more, 75 mL or more, 80 mL or more, 85 mL or more, 90 mL or more, 95 mL or more, 100 mL or more, and , ≤5000 mL, ≤4000 mL, ≤3000 mL, ≤2000 mL, ≤1000 mL, ≤900 mL, ≤800 mL, ≤700 mL, ≤600 mL, ≤500 mL, ≤400 mL, ≤300 mL, ≤200 mL, ≤150 mL.

The cell concentration (cells/mL) of the cell medicinal preparation is such that when the cell medicinal preparation is administered to a patient or subject, a therapeutic effect on the disease can be obtained as compared to a patient or subject to whom the cell medicinal preparation is not administered. It is the concentration of cells contained in the cell medicine formulation. Although the cell concentration of the cell pharmaceutical preparation is not particularly limited, for example, 1×10 ⁴ cells/mL or more, 2×10 ⁴ cells/mL or more, 3×10 ⁴ cells/mL or more, 4×10 ⁴ cells/mL or more, 5×10 ⁴ cells/mL or more, 6×10 ⁴ cells/mL or more, 7×10 ⁴ cells/mL or more, 8×10 ⁴ cells/mL or more, 9×10 ⁴ cells/mL or more, 1×10 ⁵ cells /mL or more, 2×10 ⁵ cells/mL or more, 3×10 ⁵ cells/mL or more, 4×10 ⁵ cells/mL or more, 5×10 ⁵ cells/mL or more, 6×10 ⁵ cells/mL or more, 7 × 10 ⁵ cells/mL or more, 8 × 10 ⁵ cells/mL or more, 9 × 10 ⁵ cells/mL or more, 1 × 10 ⁶ cells/mL or more, and 1 × 10 ¹⁵ cells/mL or less, 1 × 10 ¹⁴ cells/mL or less, 1×10 ¹³ cells/mL or less, 1×10 ¹² cells/mL or less, 1×10 ¹¹ cells/mL or less, 1×10 ¹⁰ cells/mL or less, 1×10 ⁹ cells/mL Below, 9×10 ⁸ cells/mL or less, 8×10 ⁸ cells/mL or less, 7×10 ⁸ cells/mL or less, 6×10 ⁸ cells/mL or less, 5×10 ⁸ cells/mL or less, 4×10 ⁸ cells/mL or less, 3×10 ⁸ cells/mL or less, 2×10 ⁸ cells/mL or less, 1×10 ⁸ cells/mL or less, 9×10 ⁷ cells/mL or less, 8×10 ⁷ cells/mL or less , 7×10 ⁷ cells/mL or less, 6×10 ⁷ cells/mL or less, 5×10 ⁷ cells/mL or less, 4×10 ⁷ cells/mL or less, 3×10 ⁷ cells/mL or less, 2×10 ⁷ Cells/mL or less, 1×10 ⁷ cells/mL or less. In addition to the above, it can be appropriately determined depending on the dosage form, administration method, purpose of use, age, body weight and symptoms of the patient or test subject.

The cell number (cells) of a cell pharmaceutical preparation is the number of cells that can obtain a therapeutic effect against a disease when the cell pharmaceutical preparation is administered to a patient or subject, compared to a patient or subject who has not been administered the cell pharmaceutical preparation. is. Although the number of cells in the cell pharmaceutical preparation is not particularly limited, for example, 1×10 ⁴ cells or more, 2×10 4 cells or more, 3× ^{10 4 cells} or more, 4×10 ⁴ cells or more, 5×10 ⁴ cells or more, 6 ×10 ⁴ cells or more, 7 × 10 ⁴ cells or more, 8 × 10 ⁴ cells or more, 9 × 10 4 cells or more, 1 × 10 ⁵ cells or more, 2 × 10 ⁵ cells or more, 3 × ^{10 5 cells} or more, 4 × 10 ⁵ cells or more, 5×10 ⁵ cells or more, 6×10 ⁵ cells or more, 7×10 ⁵ cells or more, 8×10 ⁵ cells or more, 9×10 ⁵ cells or more, 1×10 ⁶ cells or more, and , 1×10 ¹⁵ cells or less, 1×10 ¹⁴ cells or less, 1×10 ^{13 cells or less, 1×10 12 cells} or less, 1×10 ¹¹ cells or less, 1×10 ¹⁰ cells or less, 1×10 ⁹ cells or less, 9×10 ⁸ cells or less, 8×10 ⁸ cells or less, 7×10 ⁸ cells or less, 6×10 8 cells or less, 5×10 ⁸ cells or less, 4×10 ^{8 cells} or less, 3×10 ⁸ cells or less, 2 ×10 ⁸ cells or less, 1 × 10 ⁸ cells or less, 9 × 10 ⁷ cells or less, 8 × 10 7 cells or less, 7 × 10 ⁷ cells or less, 6 × 10 ⁷ cells or less, 5 × ^{10 7 cells} or less, 4 × 10 ⁷ cells or less, 3×10 ⁷ cells or less, 2×10 ⁷ cells or less, or 1×10 ⁷ cells or less. In addition to the above, it can be appropriately determined depending on the dosage form, administration method, purpose of use, age, body weight and symptoms of the patient or test subject.

The dose (cells/kg) of the cell medicinal preparation is the patient or subject who can obtain a therapeutic effect on the disease when the cell medicinal preparation is administered to the patient or subject compared to the patient or subject who is not administered the cell medicinal preparation. Or it is the number of cells per 1 kg body weight of the subject. The dose of the cell pharmaceutical preparation is not particularly limited, but for example, 1×10 ⁴ cells/kg or more, 1×10 ⁵ cells/kg or more, 5×10 ⁵ cells/kg or more, 1×10 ⁶ cells/kg or more, 2 ×10 ⁶ cells/kg or more, 4×10 ⁶ cells/kg or more, 6×10 ⁶ cells/kg or more, or 8×10 ⁶ cells/kg or more, and 1×10 ¹² cells/kg or less, 1 ×10 ¹¹ cells/kg or less, 1 × 10 ¹⁰ cells/kg or less, 1 × 10 ⁹ cells/kg or less, 5 × 10 ⁸ cells/kg or less, 1 × 10 ⁸ cells/kg or less, 8 × 10 ⁷ cells/kg or less kg or less, 6×10 ⁷ cells/kg or less, 4×10 ⁷ cells/kg or less, or 2×10 ⁷ cells/kg or less.

Cell types are not particularly limited as long as they are medically and/or pharmaceutically acceptable cells. GS cells, which are pluripotent stem cells derived from testis, EG cells derived from fetal primordial germ cells, Muse cells derived from bone marrow, etc.), somatic stem cells (bone marrow, adipose tissue, dental pulp, placenta, egg membrane, umbilical cord blood) , mesenchymal stem cells, hematopoietic stem cells, neural stem cells, etc. derived from amniotic membrane, chorion, etc.), leukocytes, monocytes, granulocytes, lymphocytes (T cells, B cells, NK cells, etc.), megakaryocytes, macrophages, nerves cells, cardiomyocytes, cardiac progenitor cells, hepatocytes, liver progenitor cells, α cells, β cells, γ cells, fibroblasts, chondrocytes, corneal cells, vascular endothelial cells, vascular endothelial progenitor cells, pericytes, etc. Alternatively, the cells may be in the form of gene introduction or in the form of knocking down target genes on the genome.

The cells used in the present invention are typically human, but also include rodents such as mice, rats and hamsters, primates such as gorillas, chimpanzees and marmosets, as well as dogs, cats, rabbits, cows and horses. , livestock such as sheep and goats, or mammals such as pets.

A pharmaceutically acceptable agent in a cell pharmaceutical preparation is not particularly limited as long as it is an aqueous medium that can maintain cells in a form that can be used as a medicine and that can be administered to animals such as humans. A pharmaceutically acceptable agent may be mixed with the cell pharmaceutical preparation at the stage of manufacturing the pharmaceutical preparation, or may be mixed with the cell pharmaceutical preparation at the stage of administering the cell pharmaceutical preparation to a patient or subject. . Pharmaceutically acceptable agents include, but are not limited to, physiological saline, electrolyte solutions, Ringer's solution, high-calorie infusions, glucose solutions, water for injection, amino acid electrolytes, and the like. In addition, pharmaceutically acceptable agents include salts, vitamins, amino acids, polysaccharides, dimethyl sulfoxide, buffers, albumin, medium, CP-1 (Kyokuto Pharmaceutical Industry Co., Ltd.), which is a cell cryoprotectant, if necessary. ), BAMBANKER (manufactured by Lymphotech), STEM-CELLBANKER (manufactured by Nihon Zenyaku Kogyo Co., Ltd.), ReproCryo RM (manufactured by ReproCell), CryoNovo (manufactured by Akron Biotechnology), MSC Freezing Solution (manufactured by Biological Industries), CryoStor (manufactured by HemaCare) and the like may be included. The medium is not particularly limited as long as it has a component composition that can be administered to animals such as humans, and includes BME medium, BGJb medium, CMRL1066 medium, Glasgow MEM medium, Improved MEM Zinc Option medium, IMDM medium (Iscove's Modified Dulbecco's Medium), Medium 199 medium, Eagle MEM medium, αMEM medium, DMEM medium (Dulbecco's Modified Eagle's Medium), Ham's F10 medium, Ham's F12 medium, RPMI 1640 medium, Fischer 's medium, and mixed medium thereof (for example, DMEM / F12 medium (Dulbecco's Modified Eagle's Medium / Nutrient Mixture F-12 Ham)), CHO-S-SFM II (Life Technologies Japan Co., Ltd.), Hybridoma - SFM (Life Technologies Japan Co., Ltd.), eRDF Dry Powdered Media (Life Technologies Japan Co., Ltd.), UltraCULTURE ^TM (BioWhittaker), UltraDOMA ^TM (BioWhittaker), UltraCHO ^TM (BioWhittaker), UltraMDCK ^TM (BioWhittaker), etc. can be used. Media such as STEMPRO (registered trademark) hESC SFM (Life Technologies Japan Co., Ltd.), mTeSR1 (Veritas), TeSR2 (Veritas) and the like can be mentioned.

Patients and subjects are typically humans, but also include, for example, rodents such as mice, rats and hamsters, primates such as gorillas, chimpanzees and marmosets, as well as dogs, cats, rabbits, cows, horses and sheep. , livestock such as goats, or non-human animals such as mammals such as pets.

The cell pharmaceutical preparation accommodated in the container for cell pharmaceutical preparation according to the present invention is drawn out through an outlet described later and administered to a patient. The route of administration to a patient is not particularly limited, and can be, for example, subcutaneous injection, intralymph node injection, intravenous injection, intraarterial injection, intraperitoneal injection, intrapleural injection, direct local injection, and the like.

The frequency of administration of the cell pharmaceutical preparation of the invention is such that a therapeutic effect can be obtained for a disease when administered to a patient or subject. The specific administration frequency can be appropriately determined depending on the dosage form, administration method, purpose of use, and age, body weight, and symptoms of the patient or subject. For example, once every 4 weeks, once every 3 weeks , once every two weeks, once a week, twice a week, three times a week, four times a week, five times a week, six times a week, or seven times a week be.

The administration period of the cell pharmaceutical preparation of the present invention is a period during which a therapeutic effect can be obtained for a disease when administered to a patient or subject. A specific administration period can be appropriately determined depending on the dosage form, administration method, purpose of use, and age, body weight, symptoms, etc. of the patient or subject. , 5 weeks, 6 weeks, 7 weeks, or 8 weeks.

The timing of administering the cell pharmaceutical preparation of the present invention to a patient or subject is not particularly limited, but is, for example, immediately after onset, within N days from onset (N represents an integer of 1 or more), immediately after diagnosis, and within N days from diagnosis. (N represents an integer of 1 or more), before remission, during remission, after remission, before relapse, during relapse, after relapse, and the like.

The cell pharmaceutical formulation of the present invention can be stored in a frozen state until immediately before use. The temperature for cryopreservation is preferably -30°C or lower, -40°C or lower, -50°C or lower, -80°C or lower, -90°C or lower, -100°C or lower, -150°C or lower, -180°C or lower, or - It is 196° C. (liquid nitrogen temperature) or less. When administering the cell pharmaceutical preparation of the present invention to a patient or subject, it can be rapidly thawed at 37°C before use.

A container for cell pharmaceutical formulations according to the present invention comprises at least a container body having an internal space capable of accommodating a liquid cell pharmaceutical formulation, and an outlet part formed with an outlet communicating with the internal space of the container body. It is good if there is

The container body is preferably made of a flexible material.
At least a part of the container body can be made of a transparent or translucent material so that the liquid surface level of the cell pharmaceutical preparation inside can be visually recognized. In particular, it is preferable that the portion of the container body provided with the first to fifth scale display portions is made of a transparent or translucent material.

Specific examples of flexible materials include soft vinyl chloride, vinyl chloride, polyurethane, ethylene-vinyl acetate copolymers, polyolefins such as polyethylene and polypropylene, styrene-butadiene-styrene copolymers or hydrogenated products thereof, and styrene. - Flexible resins such as thermoplastic elastomers such as isoprene-styrene copolymers or hydrogenated products thereof, and mixtures of thermoplastic elastomers with polyolefins and softeners such as ethylene-ethyl acrylate.

When the container body is made of a flexible resin, the container body is formed by blow-molding the resin, and two sheets composed mainly of the resin are arranged facing each other to form a peripheral edge portion. , a container body formed by folding a single sheet formed of the resin and fusing the peripheral edge portion, and an opening formed into a cylindrical shape by extrusion molding using the resin. Various forms such as a container body formed by fusing the peripheral edge of the container may be used. Although the thickness of the sheet is not particularly limited, it can be, for example, 0.2 mm to 0.6 mm. The container body is preferably a bag-shaped container having at least a portion of the wall surface formed of a sheet containing the resin as a main component. It is a bag-like container formed into a bag-like shape by joining with fusion or adhesive.

It is preferable that the cell pharmaceutical preparation container according to the present invention is formed so that the stored cell pharmaceutical preparation can be drawn out through the outlet and administered to a patient in a suspended state.

The lead-out part provided in the container for cell pharmaceutical formulations according to the present invention is not particularly limited as long as it has a lead-out port communicating with the internal space of the container body. Typically, the lead-out portion can be configured by a pipe containing a channel through which liquid can pass.

The lead-out portion preferably has a structure in which the lead-out port is closed so as to communicate with the outside. Examples of such a structure include a luer lock and a needleless port.

The dimension of the outlet provided in the lead-out part may be any size as long as the cell pharmaceutical preparation containing cells can pass through.

The number of lead-out units is not limited to one, and may be two, three, four, five, six, seven, eight, nine, ten or more, for example.

It is preferable that the container for cell pharmaceutical formulations according to the present invention further includes an introduction part formed with an introduction port that communicates the internal space of the container body with the outside. The introduction port can be used as a path for supplying a cell pharmaceutical preparation or a material for preparing a cell pharmaceutical preparation (for example, the pharmaceutically acceptable drug described above) to the internal space of the container body. can.

The introduction part is not particularly limited as long as it has an introduction port that communicates with the internal space of the container body. Typically, the introduction part can be configured by a tube containing a channel through which liquid can pass.

Moreover, the introduction part may have a structure in which the introduction port is closed so as to communicate with the outside. Examples of such a structure include a luer lock and a needleless port. Furthermore, the inlet may be irreversibly closed after the required material has been supplied to the interior space.

In addition, the number of introduction parts is not limited to one, and may be a plurality such as two, three, four, five, six, seven, eight, nine, ten or more, The internal space of the container body may be filled with the cell pharmaceutical preparation and the pharmaceutically acceptable drug via separate introduction parts and mixed. For example, when preparing a cell medicinal preparation, the container for cell medicinal preparation of the present invention includes a first introduction part for introducing the cell medicinal preparation into the internal space and a pharmaceutically acceptable drug in the internal space. and a second introduction portion for introducing into.

A feature of the container for cell pharmaceutical formulations of the present invention is that the container body is provided with one or more selected from first to fifth scale display portions. Each scale display section is composed of one or more identification displays such as visible lines, characters, signs, colors, and the like. The identification mark may be printed on the container body, may be projections and/or depressions formed on the container body, or may be a combination of printing and projections and/or depressions. .

The first scale display portion of the container for cell pharmaceutical preparations of the present invention displays the dose of the cell pharmaceutical preparation corresponding to the body weight of the patient or subject to be administered to the container body. Depending on whether the surface position is positioned at the first scale display portion or not, it is possible to visually recognize the dose of the cell pharmaceutical preparation suitable for the weight of the patient or subject. More specifically, the first scale display shows the patient or subject's dose (cells/kg) obtained by dividing the cell concentration (cells/mL) contained in the cell pharmaceutical preparation. The dose (kg/mL) of the cell pharmaceutical preparation suitable for the body weight is displayed as a scale according to the liquid volume (mL) of the cell pharmaceutical preparation. For example, the scale is arranged in stages according to the numerical value obtained by dividing the dose of the cell medicinal product from the cell concentration of the cell medicinal product and the liquid volume of the cell medicinal product, and the cell medicinal product corresponds to the body weight of the patient or subject. In order to facilitate visual recognition of the dosage of the preparation, the weight of the patient or subject to be administered, such as 10 kg, 20 kg, 30 kg, may be displayed as a numerical value near the scale. Moreover, the dose of the cell pharmaceutical preparation corresponding to the body weight of the patient or subject may be appropriately designed for each cell concentration of the cell pharmaceutical preparation to be administered to the patient or subject.

Although the numerical value of the first scale display portion is not particularly limited, for example, 0 kg, 5 kg, 10 kg, 15 kg, 20 kg, 25 kg, 30 kg, 35 kg, 40 kg, 45 kg, 50 kg, 55 kg, 60 kg, 65 kg, 70 kg, 75 kg, Any one or more of 80 kg, 85 kg, 90 kg, 95 kg, 100 kg, etc. may be selected.

It is preferable that the numerical value of the first scale display portion is displayed so as to increase toward the lead-out portion of the container body. The interval between the numerical values on the first scale display is not particularly limited, and may be appropriately designed according to the type of cells to be administered, the disease, the shape of the container, the material of the container, the capacity of the container, and the like.

The second scale display portion in the container for cell pharmaceutical preparation of the present invention displays the amount of liquid for diluting the cell pharmaceutical preparation with a pharmaceutically acceptable drug, and the liquid level in the container body is The cell concentration of the cell pharmaceutical preparation to be administered to the patient or subject can be visually recognized depending on whether or not it is positioned on the second scale display portion. More specifically, the second scale display shows the liquid volume (mL ), and the volume of the cell medicinal product before mixing plus the volume of the pharmaceutically acceptable drug to be filled is displayed as a scale. Marking lines indicating the final position of the liquid level of the formulation. Therefore, by mixing the cell pharmaceutical preparation and a pharmaceutically acceptable drug using the mark line, the cell concentration of the cell pharmaceutical preparation to be administered to the patient or subject can be easily adjusted, and the second The cell concentration of the cell pharmaceutical preparation to be administered to the patient or subject can be visually confirmed by the scale display.

The third scale display portion of the container for cell medicine preparation of the present invention displays the amount of liquid to be filled with the cell medicine preparation, and the liquid level position in the container main body is indicated by the third scale display portion. Depending on whether it is positioned or not, it is possible to visually confirm the number of cells of the cell pharmaceutical preparation to be introduced into the container body. More specifically, the third scale display portion displays the volume (mL) of the cell pharmaceutical preparation to be filled as a scale, and the volume of the cell pharmaceutical preparation to be filled in the container for the cell pharmaceutical preparation. It is a marker line that indicates the final position of the surface. Therefore, it is possible to easily fill the cell pharmaceutical preparation using the mark line, and the cell concentration (cells/mL) and filling amount (mL) of the cell pharmaceutical preparation to be filled can be confirmed. The number of cells of the cell medicine formulation to be introduced becomes visible.

The fourth scale display portion of the container for cell pharmaceutical formulation of the present invention displays the amount of liquid in the container, and whether or not the liquid surface position of the container body is positioned at the fourth scale display portion. This makes it possible to visually check the amount of the cell pharmaceutical preparation remaining in the container body. More specifically, the fourth scale display section displays the liquid volume (mL) that can be accommodated in the cell pharmaceutical preparation container as a scale in stages. For example, the amount of liquid that can be accommodated in the cell pharmaceutical preparation container is arranged in stages as a scale, and liquids such as 100 mL, 200 mL, 300 mL, etc. Amounts may be expressed as numbers.

The numerical value of the fourth scale display part is not particularly limited, but for example, 1 mL, 2 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL, 9 mL, 10 mL, 15 mL, 20 mL, 25 mL, 30 mL, 35 mL, 40 mL, 45 mL, 50 mL, 55 mL, 60 mL, 65 mL, 70 mL, 75 mL, 80 mL, 85 mL, 90 mL, 95 mL, 100 mL, 150 mL, 200 mL, 300 mL, 400 mL, 500 mL, 600 mL, 700 mL, 800 mL, 900 mL, 1000 mL, 2000 mL, 3000 mL, 4000 mL, Any one or more such as 5000 mL may be selected.

It is preferable that the numerical value of the fourth scale display portion is displayed so as to decrease toward the lead-out portion of the container body. The interval between numerical values in the fourth scale display is not particularly limited, and may be appropriately designed according to the type of cells to be administered, the disease, the shape of the container, the material of the container, the capacity of the container, and the like.

The fifth scale display portion in the container for cell pharmaceutical preparations of the present invention displays the number of cells in the cell pharmaceutical preparation to be administered to a patient or subject, and the liquid surface position in the container main body is the fifth scale display portion. It is possible to visually recognize the number of cells of the cell pharmaceutical preparation administered to the patient or subject depending on whether or not it is positioned on the scale display part of . More specifically, the fifth scale display part is obtained by multiplying the cell concentration (cells/mL) contained in the cell pharmaceutical preparation by the liquid volume (mL) of the cell pharmaceutical preparation administered to the patient or subject. The number of cells (cells) of the cell pharmaceutical preparation administered to the patient or subject is displayed as a scale according to the liquid volume (mL) of the cell pharmaceutical preparation. For example, cells administered to a patient or subject by arranging a scale according to the numerical value obtained by multiplying the cell concentration of the cell medicinal product by the liquid volume of the administered cell medicinal product and the liquid volume of the cell medicinal product. In order to facilitate visual recognition of the cell number of the pharmaceutical preparation, the number of cells administered to the patient or subject, such as 1×10 ⁴ cells, 2×10 ⁴ cells, 3×10 ⁴ cells, etc., is displayed as a numerical value near the scale. good too.

The numerical value of the fifth scale display portion is not particularly limited, but is, for example, 1×10 ⁴ cells, 2×10 ⁴ cells, 3×10 ⁴ cells, 4×10 ⁴ cells, 5×10 ⁴ cells, 6×. 10 ⁴ cells, 7×10 ⁴ cells, 8×10 ⁴ cells, 9×10 ⁴ cells, 1×10 ⁵ cells, 2×10 5 cells, 3×10 ⁵ cells, 4× ^{10 5 cells} , 5×10 ^{5 cells} cells, 6×10 ⁵ cells, 7×10 ⁵ cells, 8×10 ⁵ cells, 9×10 ⁵ cells, 1×10 ⁶ cells, 1×10 7 cells, 1× ^{10 8 cells} , 1×10 ⁹ cells, Any one or more of 1×10 ¹⁰ cells, 1×10 ¹¹ cells, 1×10 ¹² cells, 1×10 ¹³ cells, 1×10 ¹⁴ cells, 1×10 ¹⁵ cells and the like may be selected.

It is preferable that the numerical value of the fifth scale display portion is displayed so as to increase toward the lead-out portion of the container body. The interval between the numerical values on the fifth scale display is not particularly limited, and may be appropriately designed according to the type of cells to be administered, the disease, the shape of the container, the material of the container, the volume of the container, and the like.

The container for cell medicinal preparations of the present invention may be an empty form that does not contain a liquid such as a cell medicinal preparation, a form that contains a cell medicinal preparation, or a container that contains a cell medicinal preparation and a pharmaceutically acceptable drug. It can be distributed in various forms, such as a form in which the cell pharmaceutical preparation is stored, a form in which only the cell pharmaceutical preparation for preparing the cell pharmaceutical preparation is stored, and the like. The cell medicinal preparation for preparing the cell medicinal preparation is a cell medicinal preparation containing cells at a higher concentration than the cell concentration in the cell medicinal preparation prepared for treating the disease of the patient or subject. . Moreover, in this specification, "a cell pharmaceutical preparation for preparing a cell pharmaceutical preparation" may be referred to as a "high-concentration cell pharmaceutical preparation".

The cell pharmaceutical preparation or high-concentration cell pharmaceutical preparation may have been processed using a cell suspension processing apparatus equipped with a hollow fiber separation membrane module. An example of the hollow fiber separation membrane module is shown in FIG. The hollow fiber separation membrane module 800 comprises a hollow fiber separation membrane 801 and a container 810 containing it. The container 810 has an upstream head 814 formed with a liquid supply port 811 to be supplied to the hollow fiber separation membranes 801, and a treated liquid outlet 812 from which the liquid treated by the hollow fiber separation membranes 801 is led out. It also includes a body portion 816 formed with a filtrate outlet port 813 that connects with the formed downstream head portion 815 and leads out the filtrate from the hollow fiber separation membrane 801 .

A bundle 802 of a large number of hollow fiber separation membranes 801 is provided inside the body portion 816 , and a bundle 802 of the hollow fiber separation membranes 801 is placed at the upstream end of the body portion 816 , and an upstream open end 803 of the hollow fiber separation membranes 801 is provided. facing the upstream head portion 814, and filling the gaps between the adjacent hollow fiber separation membranes 801 and between the bundle 802 and the inner peripheral surface of the body portion 816, and the body portion 816. At the downstream end, the bundle 802 of the hollow fiber separation membranes 801 is fixed so that the downstream open end 804 of the hollow fiber separation membranes 801 faces the downstream head 815, and between adjacent hollow fiber separation membranes 801 and the bundle. A downstream side resin layer portion 822 is arranged to fill the gap between 802 and the inner peripheral surface of body portion 816 . The upstream end of barrel 816 is crowned by upstream head 814 and the downstream end of barrel 816 is crowned by downstream head 815 . With this configuration, the supply port 811 and the treated liquid outlet 812 are continuous via the space inside the hollow fiber separation membrane 801, and the filtrate outlet 813 is different from the supply port 811 and the treated liquid outlet 812. They are separated by membrane walls that constitute the hollow fiber separation membrane 801 and have a discontinuous structure.

The bundle 802 of the hollow fiber separation membranes 801 is preferably a bundle of approximately 10 to 1000 hollow fiber separation membranes 801 .

As the resin material constituting the hollow fiber separation membrane 801, a synthetic polymer material can be preferably used from the viewpoint of safety and stability of the material. Among these, polysulfone-based or cellulose-based hydrophilic polymeric materials can be used more preferably. Furthermore, polyethersulfone and cellulose ester are most preferably used because of their safety, stability, and availability.

In the hollow fiber separation membrane module 800 , the cell suspension supplied from the supply port 811 is introduced inside the hollow fiber separation membranes 801 from the upstream open end 803 . The introduced cell suspension passes through micropores provided in the membrane wall of the hollow fiber separation membrane 801 while filling the space inside the hollow fiber separation membrane 801 to remove contaminants on the outside of the hollow fiber separation membrane 801. A filtrate containing a liquid medium is discharged, and this filtrate is discharged out of the hollow fiber separation membrane module 800 through the filtrate discharge port 813 . On the other hand, the concentrated cell suspension inside the hollow fiber separation membrane 801 is led out of the hollow fiber separation membrane module 800 from the downstream open end 804 through the treated liquid outlet 812 . By repeating the process of passing the cell suspension through the inner space of the hollow fiber separation membrane as necessary, the cell suspension is washed, concentrated, and / or replaced with the medium, and the desired It is possible to prepare compositional cell pharmaceutical formulations or high concentration cell pharmaceutical formulations.

An example of the method for preparing the cell pharmaceutical preparation according to the present invention is
A container body filled with a cell pharmaceutical formulation and having an internal space capable of holding a liquid, a lead-out portion communicating with the internal space of the container body, and a patient or subject body weight to be administered provided in the container body. and a second scale display provided on the container body for displaying the amount of liquid for diluting the cell medicinal preparation with a pharmaceutically acceptable drug. at least the step of filling a container for cell pharmaceutical preparations having a portion with a pharmaceutically acceptable drug until the liquid level reaches the second scale display portion of the container body. In this example of the preparation method, a medicinal cell preparation having an intended cell concentration to be administered to a patient or a subject can be easily prepared using the second scale display as an index. In this example of the preparation method, examples of the cell medicinal preparation prefilled in the cell medicinal preparation container include the above-mentioned "cell medicinal preparation for preparing a cell medicinal preparation" or "high concentration cell medicinal preparation". The container for cell medicinal preparation filled with the cell medicinal preparation may be a container for cell medicinal preparation that is distributed in a form containing only the cell medicinal preparation for preparing the cell medicinal preparation, or may be an empty container for cell medicinal preparation. The container may be prepared by filling a container for cellular pharmaceutical preparations that is distributed in the form with the cellular pharmaceutical preparations for preparing the cellular pharmaceutical preparations by the user. Specific embodiments of the cell pharmaceutical preparation, the first scale display section, the second scale display section, the pharmaceutically acceptable drug, etc. are as described above.

Another example of the method for preparing a cell pharmaceutical preparation according to the present invention is
A container body having an internal space capable of holding a liquid; a lead-out portion communicating with the internal space of the container body; a first scale display portion for displaying; a second scale display portion for displaying the amount of liquid for diluting the cell medicine preparation with a pharmaceutically acceptable drug provided on the container body; a container for cell medicinal preparation having a third scale display for indicating the amount of liquid to be filled with the cell medicinal preparation, and fill the cell medicinal preparation until the liquid level reaches the third scale display of the container body. filling;
At least the step of filling the container filled with the cell pharmaceutical preparation with a pharmaceutically acceptable drug until the liquid level reaches the second scale display portion of the container body. In the first half of the steps of this example of the preparation method, the cell pharmaceutical preparation containing the intended number of cells can be filled into the cell pharmaceutical preparation container by a simple operation using the third scale display as an index. In the second half step of this example of the preparation method, a pharmaceutical cell preparation having an intended cell concentration to be administered to a patient or a subject can be easily prepared using the second scale display as an index. In this example of the preparation method, the cell medicine preparation to be filled in the first half step can be exemplified by the above-mentioned "cell medicine preparation for preparing a cell medicine preparation" or "high-concentration cell medicine preparation". Specific embodiments of the cell pharmaceutical preparation, the first scale display portion, the second scale display portion, the third scale display portion, the pharmaceutically acceptable drug, etc. are as described above. be.

Hereinafter, based on specific embodiments, the characteristics of the container for cellular pharmaceutical preparations according to the present invention and the method for preparing a cellular pharmaceutical preparation using the container for cellular pharmaceutical preparations according to the present invention will be described, but the scope of the present invention is These embodiments are not limiting.

<First embodiment>
FIG. 1 shows a cell pharmaceutical formulation container 1 (hereinafter sometimes referred to as “container 1”) according to the first embodiment of the present invention.

The container 1 includes a container body 10 , a lead-out portion 20 , a first introduction portion 30 and a second introduction portion 40 .

The container body 10 is a bag formed by arranging a pair of substantially rectangular first resin sheet 11 and second resin sheet 12 to face each other and joining the peripheral edges thereof by thermal fusion. The first resin sheet 11 and the second resin sheet 12 are sheets mainly composed of flexible resin. Specific examples of the flexible resin are as described above.

At least a part of the first resin sheet 11 and the second resin sheet 12 is made of a transparent or translucent material so that the level of the liquid level of the cell medicine preparation inside can be visually observed. ing. In addition, it is preferable that the inner surfaces of the first resin sheet 11 and the second resin sheet 12 are pear-finished so that residual liquid can be reduced at the time of administration of the cell pharmaceutical preparation.

A portion where the first resin sheet 11 and the second resin sheet 12 are joined by heat-sealing is referred to as a fused portion 13 . An internal space 14 is formed between the first resin sheet 11 and the second resin sheet 12 in the container body 10 . Note that FIG. 1 is a schematic plan view of the container 1 with the internal space 14 empty.

The lead-out portion 20 includes a lead-out pipe 22 formed therein with a lead-out port 21 serving as a path for leading the liquid contained in the inner space 14 to the outside, and a lead-out pipe 22 that communicates between the inner space 14 of the container body 10 and the outside. A luer lock 23 for communicably blocking the outlet of the tube 22 is provided.

The first introduction part 30 communicates between the internal space 14 of the container body 10 and the outside, and is formed with a first introduction port 31 serving as a path for introducing material from the outside into the internal space 14 . An introduction pipe 32 and a luer lock 33 for communicably blocking the inlet of the first introduction pipe 32 are provided.

The second introduction part 40 communicates between the internal space 14 of the container body 10 and the outside, and is formed with a second introduction port 41 serving as a path for introducing material from the outside into the internal space 14 . An introduction pipe 42 and a luer lock 43 for communicably blocking the inlet of the second introduction pipe 42 are provided.

The container main body 10 has a generally rectangular shape, and the lead-out portion 20 is formed such that one end of the lead-out pipe 22 is connected to the first resin sheet 11 and the second resin sheet 11 on one end side of the container main body 10 in the longitudinal direction. The first resin sheet 11 and the second resin sheet 12 surrounding the first resin sheet 11 and the second resin sheet 12 are joined by heat sealing to be integrated with the container body 10 . Similarly, in the first introduction part 30 and the second introduction part 40, one end of each of the first introduction pipe 32 and the second introduction pipe 42 is located at the other longitudinal end of the container body 10. It is arranged between the first resin sheet 11 and the second resin sheet 12 on the side, and the first resin sheet 11 and the second resin sheet 12 around it are joined by heat sealing to be integrated with the container body 10. has been made That is, the first introduction portion 30 and the second introduction portion 40 are arranged at the end portion of the container body 10 that faces the end portion where the lead-out portion 20 is arranged.

In the first embodiment, through-holes 15, 15 are provided in portions outside the fused portion 13 at both ends of the side of the container body 10 on which the first introduction portion 30 and the second introduction portion 40 are arranged. is formed. By hanging the container 1 on a support such as a hook through the through holes 15, 15, the first introduction part 30 and the second introduction part 40 are positioned at the upper end in the vertical direction, and the lead-out part 20 is It can be suspended so as to be located at the lower end in the vertical direction.

As shown in FIG. 1, when the container 1 is suspended so that the lead-out portion 20 is vertically downward, the opening 21A of the lead-out port 21 of the lead-out portion 20 on the side of the inner space 14 is the most in the inner space 14. The lead-out portion 20 is positioned downward, and the portion 13A of the fused portion 13 surrounding the internal space 14, which is positioned vertically downward, moves upward in the vertical direction as it moves away from the opening 21A in the horizontal direction. It is preferably formed so as to be positioned. With this configuration, the cell pharmaceutical preparation is accommodated in the internal space 14, the container 1 is suspended so that the outlet portion 20 is vertically downward, and the cell pharmaceutical preparation is led out from the outlet port 21 of the outlet portion 20 to be delivered to the patient or patient. When administered to a subject, the cells are less likely to stay in the portion 13A and more likely to move toward the opening 21A, so a cell pharmaceutical preparation containing an intended amount of cells can be administered to the patient or subject.

(First feature)
A first feature of the container 1 according to the first embodiment is that the container body 10 has a first scale display section 100 that displays the dose of the cell pharmaceutical preparation corresponding to the weight of the patient or subject to be administered, and the container It is possible to visually recognize the dose of the cell pharmaceutical preparation suitable for the patient's or subject's body weight, depending on whether or not the liquid surface position in the main body 10 is positioned at the first scale display section 100 .
The functions of the first scale display unit 100 will be specifically described with reference to FIGS. 2 and 3. FIG.

FIG. 2 schematically shows a state in which a liquid cell pharmaceutical formulation L (hereinafter sometimes referred to as “formulation L”) is accommodated and suspended in the internal space 14 of the container body 10 of the container 1 according to the first embodiment. diagrammatically. The cell concentration and liquid volume of the formulation L to be accommodated are controlled, and the formulation L is accommodated so as to have a predetermined cell concentration and liquid volume. The first scale display part 100 is arranged to extend in the vertical direction when the container 1 is suspended, and is positioned vertically below the liquid surface A of the preparation L before the start of administration when the container 1 is suspended. It includes a numerical scale 110 and a numerical value 120 that In the illustrated example, the first scale display unit 100 has a large scale 111 that indicates the weight of the patient or subject to be administered in units of 10 kg, a medium scale 112 that indicates the weight in units of 5 kg, and a small scale 113 that indicates the weight in units of 1 kg. and a numerical value 120 indicating the weight of the patient or subject corresponding to each major scale 111 . In this embodiment, the numerical value 120 of the first scale display portion 100 is displayed so as to increase toward the lead-out portion 20 of the container body 10 .

FIG. 3 shows a state in which the liquid formulation L is stored in the internal space 14 of the container body 10 of the container 1 according to the first embodiment shown in FIG. is derived and administered to a patient or a subject. When the formulation L is administered to a patient or subject, the liquid level A within the container body 10 moves downward in the vertical direction. The first scale display unit 100 displays the dose of the cell pharmaceutical preparation corresponding to the body weight of the patient or subject to be administered according to the position of the liquid surface A within the container body 10 . The body weight of the patient or subject is determined by whether or not the position of the liquid surface A of the preparation L in the container body 10 is positioned on the numerical scale 110 of the first scale display section 100 corresponding to the weight of the patient or subject to be administered. The dosage of Formulation L suitable for is visible. For example, when administering the formulation L from the container 1 to a patient or subject weighing 65 kg, as shown in FIG. By visually recognizing , it is possible to grasp that the dose of formulation L suitable for the patient's or subject's body weight has been administered.

In the medical field, the weight of the patient or subject is confirmed in advance, and with the container 1 suspended, the preparation L is passed through the outlet port 21 of the outlet portion 20, and the liquid surface A is displayed on the first scale display portion. By a simple operation of administering to the patient or subject until reaching the numerical scale 110 indicating the weight of the patient or subject in 100, and stopping the administration at the time of reaching, the appropriate number of cells according to the weight of the patient or subject A quantity of cell pharmaceutical formulation can be administered to a patient or subject. The start and stop of the administration of the preparation L through the outlet port 21 of the outlet part 20 can be achieved by connecting a channel such as a tube to the downstream of the outlet part 20, and further connecting the channel to the patient or subject. A mechanism (clamp, valve, etc.) for adjusting the opening and closing of the channel is provided in the middle of the channel, and the administration of the formulation L is started by opening the channel. The administration of the preparation L can be stopped by closing the channel, or the administration of the preparation L can be controlled by providing a pump in the middle of the channel.

According to this embodiment, it is not necessary to calculate the appropriate dose of formulation L for the patient's or subject's body weight at the medical site, thus reducing the risk of wrong dose. In addition, there is no need to take out the dosage form L according to the weight of the patient or subject from the container 1 with a syringe or the like. Since L can be administered directly, it is advantageous in that the stress applied to cells is small and the risk of damaging cells in preparation L is low, and that dosage errors are unlikely to occur because there are few steps. In addition, unlike the method described in Cited Document 2, in which the drug solution bag is sandwiched between clips to divide the cell pharmaceutical preparation so that the dose is adjusted to the body weight, in the present embodiment, the preparation L is the container 1 Since the container 1 is not divided inside, the entire preparation L can be made to flow by kneading the container 1 by hand, and the cell concentration in the preparation L can be easily maintained uniformly.

In the illustrated embodiment, the first scale display 100 only indicates patient or subject weights up to 70 kg, but may be configured to indicate greater weights. Further, when administering formulation L to a patient or subject weighing more than 70 kg and not more than 140 kg using container 1 of the illustrated embodiment, two containers 1 filled with formulation L are prepared, and from one container 1, Formulation L is administered to the patient or subject until the liquid level A reaches the numerical scale corresponding to the dose for a patient or subject weighing 70 kg, and from another container 1, the weight of the patient or subject exceeds 70 kg. Formulation L can be administered to a patient or subject until liquid level A reaches a numerical scale corresponding to .

(Second feature)
The preparation method of the formulation L is not particularly limited, but it may be prepared inside the container 1 according to the first embodiment. It may be prepared by filling and mixing with an acceptable drug L2. For use in preparing such a formulation L, the container 1 according to the first embodiment has a second feature that the container body 10 is filled with a pharmaceutically acceptable drug L2 into the internal space 14. A second scale display portion 200 for displaying the liquid volume is provided, and depending on whether or not the position of the liquid level A in the container body 10 is positioned at the second scale display portion 200, the amount of the preparation L to be administered to the patient or subject can be determined. Cell concentration is visible.

Specifically, the container 1 having the second scale display portion 200 in the container body 10 is used, and as shown in FIG. , and thereafter, as shown in FIG. 5, a pharmaceutically acceptable drug L2 can be filled until the liquid level A reaches the second scale display portion 200 . In this case, the second scale display portion 200 indicates the final position of the liquid level A in the container body 10 when the container 1 is suspended and the internal space 14 is filled with the pharmaceutically acceptable drug L2. It is a landmark line.

As shown in FIG. 4, a container 1 according to the first embodiment pre-filled with a high-concentration cell pharmaceutical preparation L1 is prepared, and a pharmaceutically acceptable drug L2 is filled and mixed at a medical site. When preparing the formulation L, the cell concentration in the formulation L can be visually recognized by checking whether the liquid surface A of the liquid in the container body 10 is positioned at the second scale display portion 200 . By providing the second scale display portion 200, it is easy to accurately fill the intended amount of the pharmaceutically acceptable drug L2 and prepare the preparation L with the intended cell concentration.

In the illustrated embodiment, the second scale display portion 200 is a line that extends in a horizontal direction when the container 1 is suspended and that is formed over substantially the entirety of the container body 10 in this direction. is not limited to For example, the second scale display portion 200 extends in the horizontal direction when the container 1 is suspended.

When the internal space 14 of the container body 10 of the container 1 is filled with the high-concentration cell pharmaceutical preparation L1 and the pharmaceutically acceptable drug L2 and mixed, the first introduction part 30 and the second introduction part 40 One of them can be filled with the high-concentration cell medicine preparation L1, and the other can be filled with the pharmaceutically acceptable drug L2. In addition, one or both of the first introduction part 30 and the second introduction part 40 used for filling the high-concentration cell pharmaceutical preparation L1 or the pharmaceutically acceptable drug L2 are irreversibly blocked after filling. good too.

(Third feature)
In the container 1 according to the first embodiment, the container body 10 is provided with a third scale display portion 300 that displays the amount of liquid filled with the preparation L or the high-concentration cell medicine preparation L1. The third feature is that the number of cells in the preparation L or high-concentration cell medicine preparation L1 to be introduced into the container body 10 can be visually recognized depending on whether or not the position of is positioned in the third scale display portion 300.

In the example shown in FIG. 4 , the third scale display section 300 suspends the container 1, and when the internal space 14 of the container body 10 is filled with the high-concentration cell medicine preparation L1, the liquid of the high-concentration cell medicine preparation L1 is displayed. The surface A is a mark line indicating the position to be filled.

As shown in FIG. 4, by filling the container 1 according to the first embodiment with the high-concentration cell pharmaceutical preparation L1 until the liquid level A reaches the third scale display portion 300, a high concentration containing the intended number of cells is obtained. Concentration cell pharmaceutical preparation L1 can be accurately filled. Furthermore, as shown in FIG. 5, by filling and mixing the pharmaceutically acceptable drug L2 until the liquid level A reaches the second scale display portion 200, the preparation L with the intended cell concentration is prepared. be able to. In addition, when the container 1 is suspended, depending on whether or not the liquid surface A of the high-concentration cell pharmaceutical preparation L1 in the container body 10 is positioned at the third scale display portion 300, the high-concentration cells containing an appropriate number of cells can be determined. It is possible to visually confirm whether or not the pharmaceutical preparation L1 is stored.

In the illustrated embodiment, the third scale display portion 300 is a line that extends in a horizontal direction when the container 1 is suspended and that is formed over substantially the entirety of the container body 10 in this direction. is not limited to For example, the third scale display portion 300 extends in the horizontal direction when the container 1 is suspended.

In the container 1 according to the first embodiment, the second scale display part 200 and the third scale display part 300 are arranged parallel to each other, so that the high-concentration cell pharmaceutical preparation L1 and the pharmaceutically acceptable It is easy to visually recognize the filling amount of the drug L2.

<Second embodiment>
FIG. 6 shows a cell pharmaceutical formulation container 1 (hereinafter sometimes referred to as "container 1") according to a second embodiment of the present invention.

In the container 1 according to the second embodiment, the same reference numerals are assigned to the configurations common to the container 1 according to the first embodiment, and the description thereof is omitted.

In the container 1 according to the second embodiment shown in FIG. 6, the container body 10 is provided with a fourth scale display portion 400 that displays the amount of liquid in the container body 10, and the position of the liquid surface A of the container body 10 is the fourth scale display portion 400. 4, the liquid amount of the preparation L remaining in the container main body 10 can be visually recognized depending on whether or not it is positioned at the scale display portion 400 of No. 4.

The fourth scale display portion 400 is arranged to extend in the vertical direction when the container 1 is suspended. It includes a numerical scale 410 and a numerical value 420 indicating the volume below plane A. FIG. In this embodiment, the numerical value 420 of the fourth scale display portion 400 is displayed so as to decrease toward the lead-out portion 20 of the container body 10 .

By providing the fourth scale display part 400, when the formulation L is administered from the container 1 containing the formulation L to the patient or the subject through the outlet 21, the liquid amount of the formulation L remaining in the container 1 can be visually recognized. can do. When administering the formulation L from the container 1 to a patient or a subject, if the remaining liquid amount of the formulation L corresponding to an appropriate dose according to the body weight of the patient or the subject is known in advance, the remaining liquid of the formulation L can be obtained. It is possible to confirm the dosage based on the amount, and in conjunction with confirmation based on the patient's or subject's weight using the first scale display 100, it is possible to double confirm the dosage of the formulation L. Become. This makes it possible to more safely administer to the patient or subject the preparation L containing an appropriate number of cells according to the weight of the patient or subject.

<Third Embodiment>
FIG. 7 shows a cell pharmaceutical formulation container 1 (hereinafter sometimes referred to as "container 1") according to a third embodiment of the present invention.

In the container 1 according to the third embodiment, components common to those of the container 1 according to the first embodiment and the container 1 according to the second embodiment are denoted by the same reference numerals, and description thereof is omitted.

In the container 1 according to the third embodiment shown in FIG. The number of cells in the preparation L administered to the patient or subject can be visually recognized depending on whether or not the position of the liquid surface A of is positioned on the fifth scale display portion 500 .

The fifth scale display portion 500 is arranged to extend in the vertical direction when the container 1 is suspended, and is positioned vertically below the liquid surface A of the preparation L before the start of extraction when the container 1 is suspended. Includes numeric scale 110 and numeric 520 . Here, the numerical scale 110 also serves as the numerical scale 110 of the first scale display section 100 . Of the numerical scale 110, the large scale 111 indicates the weight of the patient or subject to be administered in units of 10 kg, and the number of cells contained in the administered formulation L in units of 2×10 ⁷ . , indicates the weight of the patient or subject to be administered in units of 5 kg, and indicates the number of cells contained in the administered preparation L in units of 1×10 ⁷ , and the minor scale 113 indicates the weight of the patient or subject to be administered. is shown in units of 1 kg, and the number of cells contained in the administered formulation L is shown in units of 2×10 ⁶ cells. Numerical values 520 indicate the number of administered cells corresponding to each major scale 111 . In this embodiment, the numerical value 520 of the fifth scale display portion 500 is displayed so as to increase toward the lead-out portion 20 of the container body 10 .

Although not shown, the fifth scale display section 500 may be a scale display section independent of the first scale display section 100 .

By providing the fifth scale display part 500, when the formulation L is drawn out from the container 1 containing the formulation L through the outlet 21 and administered to a patient or a subject, the liquid level of the formulation L in the container body 10 The number of cells administered to the patient or subject can be visually recognized by checking whether the position of A is located on the numerical scale 110 corresponding to the number of administered cells of the fifth scale display section 500 . When administering the preparation L from the container 1 to the patient or subject, if the number of cells to be administered to the patient or subject is known in advance, the dose can be determined appropriately by referring to the fifth scale display section 500. In addition to confirmation based on the weight of the patient or subject using the first scale display section 100, it is possible to double confirm the dose of the formulation L. This makes it possible to more safely administer to the patient or subject the amount of preparation L containing the number of cells to be administered to the patient or subject.

1: Container for cell pharmaceutical preparation 10: Container main body 14: Internal space 20: Outlet part 21: Outlet ports 30, 40: Inlet parts 31, 41: Inlet port 100: First scale display part 200: Second scale display Part 300: Third scale display part 400: Fourth scale display part 500: Fifth scale display part L: Cellular medicinal preparation L1: Cellular medicinal preparation for preparing a cellular medicinal preparation (high-concentration cellular medicinal preparation)
L2: pharmaceutically acceptable drug A: liquid level

All publications, patents and patent applications cited herein are hereby incorporated by reference in their entirety.

Claims (13)

A cell pharmaceutical preparation container,
a container body having an internal space capable of holding a liquid;
a lead-out portion that communicates with the internal space of the container body;
The container body includes a first scale display portion for displaying the dose of the cell pharmaceutical preparation corresponding to the weight of the patient or subject to be administered,
Depending on whether the liquid surface position in the container body is positioned at the first scale display portion, the dosage of the cell pharmaceutical preparation suitable for the patient's or subject's body weight can be visually recognized ,
The numerical value of the first scale display portion is displayed so as to increase toward the lead-out portion of the container body,
The container body is made of a flexible material,
Said container. Further, the container main body includes a second scale display portion for displaying the amount of liquid for diluting the cell pharmaceutical preparation with a pharmaceutically acceptable drug, and the liquid level position in the container main body corresponds to the second scale. 2. The container according to claim 1, wherein the cell concentration of the cell pharmaceutical preparation to be administered to the patient or subject can be visually recognized depending on whether it is positioned on the display portion. Further, the container main body has a third scale display portion for displaying the amount of liquid to be filled with the cell pharmaceutical preparation, and whether or not the liquid surface position in the container main body is positioned at the third scale display portion. 3. The container according to claim 1 or 2 , wherein the number of cells in the cell pharmaceutical preparation to be introduced into the container body can be visually confirmed. Further, the container main body has a fourth scale display portion for displaying the amount of liquid in the container. The container according to any one of claims 1 to 3 , wherein the liquid amount of the cell pharmaceutical preparation remaining in the container can be visually confirmed. 5. The container according to claim 4 , wherein the numerical value of said fourth scale display portion is displayed so as to decrease toward the lead-out portion of said container body. Further, the container main body has a fifth scale display portion for displaying the number of cells of the cell pharmaceutical preparation administered to the patient or subject, and the liquid surface position in the container main body is indicated by the fifth scale display portion. The container according to any one of claims 1 to 5 , wherein the number of cells of the cell pharmaceutical preparation administered to the patient or subject can be visually confirmed depending on whether or not the container is positioned. 7. The container according to claim 6 , wherein the numerical value of said fifth scale display portion is displayed so as to increase toward the lead-out portion of said container body. The container main body has a second scale display portion for displaying the amount of liquid for diluting the cell pharmaceutical preparation with a pharmaceutically acceptable drug, and a third scale display for displaying the amount of liquid for filling the cell pharmaceutical preparation. and
The cell concentration of the cell pharmaceutical preparation to be administered to the patient or subject can be visually recognized depending on whether the liquid surface position in the container body is positioned at the second scale display portion,
The number of cells in the cell pharmaceutical preparation to be introduced into the container body can be visually recognized by checking whether the liquid surface position in the container body is positioned at the third scale display portion,
The container according to any one of claims 1 to 7 , wherein the second scale display portion is provided on a line parallel to the third scale display portion. The container according to any one of Claims 1 to 8 , further comprising an introducing portion communicating with the internal space of the container body. 10. The container according to claim 9 , wherein the introduction portion is provided at the upper end portion of the container body facing the outlet portion. The container according to claim 9 or 10, comprising a plurality of said introduction parts. A method for preparing a cell pharmaceutical formulation, comprising:
A container body filled with a cell pharmaceutical formulation and having an internal space capable of holding a liquid, a lead-out portion communicating with the internal space of the container body, and a patient or subject body weight to be administered provided in the container body. and a second scale display provided on the container body for displaying the amount of liquid for diluting the cell medicinal preparation with a pharmaceutically acceptable drug. a portion, wherein the numerical value of the first scale display portion is displayed so as to increase toward the lead-out portion of the container body, and the container body is made of a flexible material. The method, comprising the step of filling a container for pharmaceutical preparation with a pharmaceutically acceptable drug until the liquid level reaches the second scale display portion of the container body. A method for preparing a cell pharmaceutical formulation, comprising:
A container body having an internal space capable of holding a liquid; a lead-out portion communicating with the internal space of the container body; a first scale display portion for displaying; a second scale display portion for displaying the amount of liquid for diluting the cell medicine preparation with a pharmaceutically acceptable drug provided on the container body; a third scale display portion for displaying the amount of liquid to be filled with the cell pharmaceutical preparation , wherein the numerical value of the first scale display portion is displayed so as to increase toward the lead-out portion of the container body. a step of filling the cell pharmaceutical preparation into the cell pharmaceutical preparation container, the container main body of which is made of a flexible material, until the liquid level reaches the third scale display portion of the container main body; ,
filling the container filled with the cell pharmaceutical preparation with a pharmaceutically acceptable drug until the liquid level reaches the second scale display portion of the container body.

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